Assessing a cut-off point for the diagnosis of abnormal uterine bleeding using the Menstrual Bleeding Questionnaire (MBQ): a validation and cultural translation study with Brazilian women

ABSTRACT BACKGROUND: Abnormal uterine bleeding (AUB) is a common condition, and the Menstrual Bleeding Questionnaire (MBQ) is used for its assessment. OBJECTIVES: To translate, assess the cut-off point for diagnosis, and explore psychometric properties of the MBQ for use in Brazilian Portuguese. DESIGN AND SETTING: Prospective cohort study including 200 women (100 with and 100 without AUB) at a tertiary referral center. METHODS: MBQ translation involved a pilot-testing phase, instrument adjustment, data collection, and back-translation. Cut-off point was obtained using receiver operating curve analysis. Menstrual patterns, impact on quality of life due to AUB, internal consistency, test-retest, responsiveness, and discriminant validity were assessed. For construct validity, the Pictorial Blood Assessment Chart (PBAC) and World Health Organization Quality of Life – abbreviated version (WHOQOL-BREF) were applied. RESULTS: Women with AUB were older, had higher body mass indices, and had a worse quality of life during menstruation. Regarding the MBQ's psychometric variables, Cronbach's alpha coefficient was > 0.70 in all analyses, high intraclass correlation coefficient was found in both groups; no ceiling and floor effects were observed, and construct validity was demonstrated (correlation between MBQ score, PBAC score, and clinical menstrual cycle data). No difference between MBQ and PBAC scores were perceived after the test-retest. Significant differences were found between MBQ and PBAC scores before and after treatment. An MBQ score ≥ 24 was associated with a high probability of AUB; accuracy of 98%. CONCLUSION: The MBQ is a reliable questionnaire for Brazilian women. The cut-off ≥ 24 shows high accuracy to discriminate AUB.

also the experience of women. The Institute National Health and Care Unit of the United Kingdom recommendations reinforce that intervention for abnormal bleeding must be focused on improving the QOL and not just controlling the blood loss. 3 Thus, instruments have been suggested for both aspects (blood loss and QOL).
The dosage of alkaline hematin (AH) and graphical methods are widely used for quantitative evaluation. These tools correlate the visual appearance of the loss of menstrual fluid in standardized sanitary products to the volume estimated in milliliters. 10 Examples are the Pictorial Blood Assessment Chart (PBAC) and menstrual pictogram. [11][12][13] When menstrual symptoms are only assessed, there is a questionnaire called The Menstrual Evaluation Questionnaire, which includes statements about menstrual symptoms. 14 However, these tools have limitations. AH requires the storage of sanitary products for further laboratory analysis; graphic methods do not include sanitary products, such as menstrual collectors, diapers, cloth pads, and menstrual panties. Moreover, instruments that exclusively assess symptoms cannot objectively assess the blood loss. Additionally, such instruments do not assess the possible social impact, may be affected by the patient's memory, do not distinguish between chronic and intermittent symptoms, or specifically assess the QOL. 10 There are general questionnaires to assess the QOL, such as the Medical Outcomes Study 36-Item Short Form Heath Survey (SF-36) and the World Health Organization Quality of Lifeabbreviated version (WHOQOL-bref); questionnaires for AUBspecific causes, such as uterine fibroids, have been published. 14,15 Specific questionnaires capable of assessing menstrual symptoms and the impact of AUB on women's QOL have been studied, such as the Menorrhagia Multiattribute Scale, the Menstrual Impact Questionnaire, and the Menstrual Bleeding Questionnaire (MBQ); none of them are validated for use in Brazil. [16][17][18][19] Comparative analyzes between these instruments suggest that they are capable of quantifying the blood loss and providing a qualitative assessment of the QOL. 10

OBJECTIVE
This study aimed to translate and culturally validate the first instrument capable of associating both qualitative and quantitative assessments of AUB for use in Brazilian women, in addition to assessing a cut-off point for the diagnosis of AUB.

Translation and validation of the MBQ
We have followed the methodology described in the Guidelines for the process of intercultural adaptation of self-report measures 20 and the Guidelines for Reliability and Agreement Study Reports. 21 Permission and consent for translation and validation of the MBQ was obtained by email from Dr.
Matteson. 19 Subsequently, the MBQ was translated from English into Brazilian Portuguese, through notarized translation, by two different native translators from Brazil with proficiency in English and official authorization to translate scientific documents One translator knew the questionnaire concepts, whereas the second translator did not. Subsequently, the synthesis of the two translated versions was performed, which was back-translated to English ("back-translation") by a third translator, who was unaware of the original version of the MBQ. After confirming agreement between the retranslated instrument and its original version, the MBQ was analyzed by an expert panel (GPR, LGOB, and CLBP). A face-to-face pre-test was then carried out (preliminary pilot testing) with the application of the MBQ in 30 women to assess the need for new adaptations (which were not necessary). After completing all recommended steps, the instrument was applied for validation.

Study design and participants (inclusion/exclusion criteria)
A prospective cohort study was carried out at a tertiary, academic-affiliated, outpatient clinic at the Department of Obstetrics For the control group (n = 100), women without any history of menstrual disorders since menarche and without complaints of AUB were included, that is, with menstrual cycle within the limits considered normal according to the same criteria of FIGO (frequency of cycles between 24 and 38 days, duration of flow less than or equal to 8 days, adequate blood volume, according to the woman's impression, and absence of intermenstrual bleeding).
The controls were not matched to the patients. For both groups, the menstrual pattern reported by participants was considered before using any contraceptive method, excluding iatrogenic causes of AUB or normal cycles secondary to anovulatory methods, such as combined oral contraceptives. In both groups, women should refer to the use of only regularly sized pads to reduce bias, and be between 18 and 55 years of age, following criteria used in the elaboration of the MBQ by Matteson. 19 Patients in the AUB group were recruited from the Abnormal Uterine Bleeding and surgical gynecology outpatient clinics, while control group patients were recruited from the Family Planning outpatient clinic. The exclusion criteria for both groups were as follows: conditions that prevented the reading and/or understanding of the instruments and women diagnosed with AUB already undergoing clinical or surgical treatment (oral contraceptives, intrauterine device of levonorgestrel, laparotomy, laparoscopy, hysteroscopy, or other) in order to avoid treatment bias.

MBQ
The MBQ 19 consists of 20 questions, with the evaluation of four main domains -quantity ("heaviness"), pain, irregularity, and QOL, providing a score. The higher the score, the more negative the impact of bleeding on the QOL. However, there is no established cutoff for the diagnosis of AUB, with only an average score that allows the characterization of the existence of increased bleeding associated with menstrual irregularities. We aimed to translate and culturally validate the MBQ instrument for Brazilian Portuguese using psychometric variables. We also compared the MBQ with a graphic method (PBAC), to determine whether both tools were correlated. 20,21

PBAC
The visual system represents a graduated series of sanitary pads (external and internal) with drawings representing the amount of menstrual blood. Women were asked to choose the number of pads used in the bleeding cycle according to the amount of blood depicted in the graphic representation; the greater the amount of blood represented in the pad, the higher the score.
Traditional graph described by Higham et al., 11 with a cut-off of > 100 points, was used. PBAC was used to assess the construct validity of the MBQ regarding quantitative pattern of blood loss.

WHOQOL-BREF
Developed by the World Health Organization to assess the QOL, and modified as a 26-question tool divided into four domains: physical, psychological, social relationships, and environment.
It can be used in healthy populations and in those affected by chronic diseases. The answers followed a Likert scale (1-5); the higher the score, the better the QOL. 23 It was used to assess the construct validity of MBQ regarding its impact on the QOL.

Validation -psychometric variables
All women answered a sociodemographic form and questions regarding their menstrual patterns (cycle duration, days of menstrual flow, number of pads used, need to change clothes due to blood overflow during menstruation, occurrence of bleeding after sexual intercourse, and intermenstrual bleeding). Furthermore, information Table 1. Clinical characteristics of women with (n = 100) and without (n = 100) abnormal uterine bleeding With AUB (mean ± SD) or n (%) regarding the history of anemia, need for blood transfusion due to uterine bleeding, and self-perceived impact of menstruation on QOL were collected. The MBQ, PBAC, and WHOQOL-BREF instruments were used for all women. MBQ and PBAC were reapplied to 30 women, randomly selected from the sample four weeks after the first interview and without any intervention, to assess testretest. The MBQ was reapplied to 37 women from the AUB group, four weeks after starting treatment, which could be oral combined contraceptives, oral progestins, levonorgestrel intrauterine device, anti-inflammatory or antifibrinolytic, to assess the responsiveness. 20,21 Other psychometric variables were internal consistency (degree of interrelationship between items), content validity, "floor"

Without AUB (mean ± SD) or n (%) P
and "ceiling" effect (how much the content of a measure is adequate to reflect global content), discriminant validity between case and control groups, and construct validity (fundamental form of instrument validation, as it checks whether the test measures an attribute or quality that is not operationally defined).

Statistical analysis
There was no defined sample size pattern for the validation stud- A receiver operating curve (ROC) analysis was used to obtain the cutoff point for MBQ score capable of discriminating the presence of AUB. The significance level was set at 5% (P < 0.05) for all calculations. All data were tabulated in Microsoft Excel using a spreadsheet and analyzed using SAS version 9.4 program (Cary, North Carolina, United States). Table 1 presents the baseline characteristics of the women included in the study. Women with AUB presented a higher mean age (38.4 ± 9.6 versus 30.6 ± 8. 4 years; P < 0.001) and body mass index (28.3 ± 6.3 versus 25.0 ± 5.0 kg/m 2 ; P < 0.001).

RESULTS
They also presented more comorbidities than control group.
The most common causes of AUB were leiomyomas (29%) and adenomyoses (15%). Women with AUB presented shorter menstrual cycles (22.8 ± 6.5 versus 27.8 ± 2.79 days; P < 0.001, longer blood flow duration (9.7 ± 6.9 versus 4.7 ± 0.8 days; P < 0.001) and used more menstrual pads per menstrual cycle (40.0 ± 44.0 versus 10.0 ± 4.3; P < 0.001). Additionally, women with AUB more frequently reported the association of more than one type of sanitary product to contain the bleeding, with a higher frequency of changing their underwear (95% versus 9%; P < 0.001), change of usual clothes (92% versus 4%; P < 0.001), and change of sheets and bedding (80% versus 3%; P < 0.001) due to blood overflow. The prevalence of bleeding outside the menstrual period and sinus bleeding was also higher in women with AUB  Table 2); these data display the discriminant validity for both instruments to differentiate the case and control groups.
Regarding the psychometric variables for the MBQ, Cronbach's alpha coefficient was significantly above 0.70 for the total sample, by group, and in the case group retest demonstrated internal consistency ( Table 3). There was no significant difference between initial application and the reapplication of MBQ and PBAC between women with AUB without intervention and women in the control group, indicating the test-retest reliability of both questionnaires (P = ns). The agreement between the questionnaires was also verified using the ICC ( Table 4) however, for the AUB group, the MBQ did not correlate with the total score and subdomains of the WHOQOL-BREF ( Table 5).
Responsiveness was demonstrated before and after treatment using MBQ and PBAC scores (        (Figure 1).

DISCUSSION
When treating women with complaints of abnormal uterine bleeding, health professionals must be alert to assess not only the physical repercussions of bleeding, but also the woman's experience with such disorders and its reflection in the worsening of their QOL. The MBQ assesses the AUB quantitatively and qualitatively; however, it has not been validated for use in Brazil.
This study showed that the cultural translation of the MBQ is a reliable and valid tool with high internal consistency, temporal stability, construct validity, and responsiveness to treatment.
Furthermore, it was easy to use. Our study was also able to calculate a cut-off point for the MBQ instrument, which is capable of accurately discriminating the presence of increased bleeding.
The MBQ also allows for the evaluation of response to treatment by comparing the scores before and after the therapy.
The MBQ was validated against one of the most commonly used tools in gynecological practice (PBAC) with high convergent validation. The PBAC is widely used to quantitatively assess the blood loss, owing to its easy understanding, with studies showing that scores between 50 and 185 points are associated with increased bleeding, 22 with 100 points as the most common cut-off value used in most countries. 11 Correlation between MBQ scores and those obtained from the PBAC for the total sample and in both groups individually shows that MBQ is an instrument that shows quantitative differences related to uterine bleeding.  less specific. Other tools with the approach of all four domains of the MBQ are currently unavailable, and general QOL assessment tools have a global evaluation, which can explain the absence of correlation between these tools. Thus, we believe that the MBQ, as it encompasses situations exclusively related to AUB, may be a preferable tool for assessing QOL during increased bleeding. 10,19 Considering the high prevalence of AUB in the female population, changes in diagnostic criteria, and the need for tools that help quantitatively and qualitatively in the diagnosis and reassessment of treatment, this study validated the Brazilian Portuguese language as the first questionnaire to assess AUB with a good sample size and compared the MBQ with questionnaires already validated and used to assess AUB and QOL. Another important point is the suggestion of a cut-off point to discriminate AUB and the calculation of the main psychometric variables, demonstrating a robust process of questionnaire validation. 20,21 As weaknesses: sociodemographic differences between groups may have interfered in the results, is necessary to compare the MBQ with other QOL instruments and short assessment period for responsiveness (four weeks), indicating the need for future studies with women followed up for a longer period with different interventions. The application of the MBQ to a larger population of Brazilian women will also be able to robustly demonstrate our results.

CONCLUSION
Finally, we believe that the MBQ is a valid, reliable, and stable tool that can be used to assess, diagnose, and follow up AUB treatments in Brazilian Portuguese women. It is important to evaluate women with AUB using validated, standardized questionnaires.
Considering the high prevalence of AUB and the economic reality in Brazil, the implementation of a free tool for AUB diagnosis and treatment assessment may help improve the approach to this health condition.